Calicivirus delivers vaccines in humans

Calicivirus infects rabbits. It causes a haemorrhagic disease. The rabbit bleeds from orifices and dies quickly. Humans are not a natural host for calicivirus so it does not cause infection, so the virus can be used as a vehicle for introducing antigens or proteins from infectious diseases and tumours into humans. The aim is to make and test vaccines against tumours. Eventually it is hoped to make a vaccine for a tumour which will kick the immune system and make it think there is an infectious disease.

Transcript

Sarah Young: The virus infects rabbits, that's the natural host, and it causes a haemorrhagic disease. So basically they bleed out of orifices and they die very quickly. But we are using it in our own research in humans, and humans aren't a natural host of calicivirus so it doesn't cause a productive infection in humans but we can use it as a vehicle to introduce different antigens for infectious diseases and tumours into the human host.

Robyn Williams: I don't look like a rabbit but mammals are pretty much the same. I'm rather surprised that you can tell me that a calicivirus, which you use as a sort of Trojan horse to get another kind of vaccine into my body, won't affect me in any way. How do you know?

Sarah Young: We've tried it in cells. So it doesn't cause an active infection and cause killing or lysis of cells in a culture. It doesn't do that with human cells, and that's the way we know. And we also know obviously the farmers that released them in Otago in New Zealand here, none of them got a productive infection or got any sign of disease and they were introducing huge virus titres into the environment.

Robyn Williams: And of course what you need to do is get the vaccine to the right place in the human body, and I've heard of some people who've used even a denatured AIDS virus.

Sarah Young: Yes, people are using attenuated viruses, so denatured or heat-killed viruses. So they're viruses and they're used in routine...for example, the influenza vaccine. Denatured viruses are used a lot in vaccines, so they can't infect a cell but they can provide all the proteins that you might make an immune response to.

Robyn Williams: And they can get in.

Sarah Young: They can get into your body when you inject through a needle. However, it's your phagocytic cells, certain cells that will pick it up and eat them, and that's how they get into the cells.

Robyn Williams: What would happen if you just squirted the vaccine in without that carrier?

Sarah Young: We've tried this with the virus-like particle. We have a project looking at transcutaneous vaccination and also vaccination across the mucosa, so up the nose for example, and we know that we need some sort of adjuvant to help it get across that layer of skin or the mucous membrane.

Robyn Williams: And what sort of vaccines are you taking into people?

Sarah Young: The main thrust of our research a the moment is to use these virus-like particles as carriers for tumour proteins, and we're trying to make tumour therapies and also vaccines against tumours, so to prevent tumours. So we've got those in pre-clinical trials at the moment where we're using them in vitro cultures, but the idea is that we'll use them eventually in humans. So we'll initially make tailor-made vaccines. So I've got a collaboration with my old work in the UK, Cancer Research UK, where a patient will come in, we'll [recept] out the tumour, we'll load those tumour antigens onto the VLP and then we'll use that to reinject back into the patient to try and tickle their immune system along and generate a strong immune response to that particular tumour that they've got.

Robyn Williams: And by their extract of tumour they'll kill the tumour themselves in the end.

Sarah Young: Yes, that's exactly right. So we're trying to make the immune response seem like an infectious disease, so normally you get quite tolerised to your own tumour, and tumours have ways of dampening down the immune response. So you need something to really kick the immune response into gear, and this is the way that we do that.

Robyn Williams: Is it working?

Sarah Young: We haven't tried in vivo yet, but it's certainly looking good in the animal models that we've got of tumours. We've got it working very nicely in a melanoma model, and we are trying it in some colorectal models as well, but we've just got another lot of research money to do exactly that. So basically if you were to ask me this question in another two years time, I might be able to answer it.

Robyn Williams: That's a date! Dr Sarah Young is a microbiologist at the University of Otago in New Zealand.

Guests

Sarah Young

Research Fellow Department of Microbiology and Immunology University of Otago Dunedin New Zealand